System and method of treating stuttering by neuromodulation

ABSTRACT

Stuttering-treatment techniques using neural stimulation and/or drug delivery. One or more electrodes and/or a catheter are implanted adjacent to sites in the brain. A signal generator and the electrode deliver stimulation to a first site. A pump and the catheter deliver one or more therapeutic drugs to a second site. The first and second sites could be: the supplementary motor area, the centromedian circuit, the dorsomedial nuclei, the lateral prefrontal circuit, or other paramedian thalamic and midbrain nuclei. The stuttering treatment could be performed via periodic transcranial magnetic stimulation. A sensor, located near the patient&#39;s vocal folds, can be used for generating a signal responsive to activity of the patient&#39;s speech-producing muscles. A controller adjusts one or more stimulation parameters in response to the signal from the sensor.

RELATED APPLICATIONS

This application is a Divisional application of U.S. application Ser.No. 10/001,751, filed Oct. 31, 2001. The entire content of this U.S.application is incorporated herein by reference.

FIELD OF THE INVENTION

The invention relates to therapeutic treatment of stuttering. Moreparticularly, the invention relates to treating stuttering via neuralstimulation and drug therapy techniques.

BACKGROUND OF THE INVENTION

Stuttering is a speech-disfluency problem that can have significantdevelopmental and social impacts upon stuttering individuals. Stutteringcan include repetitions of parts of words and/or whole words,prolongation of sounds, interjections of sounds or words, and undulyprolonged pauses.

Conventional stuttering treatment techniques typically focus on alertingthe patient that stuttering is occurring and having the patient try tomodify their breathing and/or speech patterns in an attempt to avoidstuttering. For instance, U.S. Pat. No. 4,020,567, entitled Method andStuttering Therapy Apparatus, issued to Webster on May 3, 1977,discloses a system for helping individuals determine when they arestuttering. The system generates an electrical signal based on theperson's speech and uses the signal to detect certain speechcharacteristics corresponding to stuttering. A first embodiment detectsspeech onset errors during the first 100 milliseconds of syllablepronunciation. In a second embodiment, stuttering is detected byevaluating the rate of change in the amplitude of the person's speech.An LED is illuminated to notify a system-user that stuttering isoccurring. The system disclosed by Webster is intended for use bystutterers while they practice learning not to stutter.

U.S. Pat. No. 4,662,847, entitled Electronic Device and Method for theTreatment of Stuttering, issued to Blum on May 5, 1987, discloses anelectronic device for treating stuttering. The device transmitselectronic speech signals from a microphone to an earphone through twopaths. One path is synchronous. The other path is asynchronous. Duringnormal speech, the synchronous speech signal is transmitted to theearphone. At any pause in phonation, the device switches to theasynchronous path and transmits speech in a delayed auditory feedbackmode until a change in the user's speech occurs.

U.S. Pat. No. 4,784,115, entitled Anti-Stuttering Device and Method,issued to Webster on Nov. 15, 1988, discloses an anti-stuttering devicefor enhancing speech fluency. The device detects vocal pulses generatedby the opening and closing of a speaker's vocal folds. Electricalsignals representative of the vocal pulses are transmitted to a receiverin the speaker's sealed ear canal where these signals are reproduced asaudio pulses. The device reduces stuttering by providing an earlyindication of the characteristics of the speaker's voice via audiopulses. The audio pulses produce a resonant effect within the person'sear canal.

U.S. Pat. No. 5,794,203, entitled Biofeedback System for SpeechDisorders, issued to Kehoe on Aug. 11, 1988, discloses a biofeedbacksystem for speech disorders that detects disfluent speech and providesauditory feedback to enable fluent speech. The disfluent-speech detectorcan be either an electromyograph (EMG) or an electroglottograph (EGG).EMG is a system that measures the electrical activities of musclesthrough electrodes attached to a person's body. EGG records the openingand closing of a person's vocal folds. EGG's use two electrodes on aperson's neck and measure the resistance between the electrodes. Thisresistance changes as the vocal folds open and close. An EGG can showthe frequency of the vocal folds. This is the fundamental pitch of theuser's voice, without the harmonics produced by the nasal cavities,mouth, and the like.

The system disclosed by Kehoe includes an electronic controllerconnected to an EMG and frequency-altered auditory feedback (FAF)circuit. The controller receives data from the EMG regarding muscletension in the user's vocal cords, masseter, and/or otherspeech-production muscles. The controller then controls the pitch of theFAF circuit in accordance with the user's muscle tension. The user wearsa headset with a microphone and headphones. Three EMG electrodes aretaped onto the user's neck and/or jaw. When the user speaks fluently,with speech-production muscles relaxed, the user's hears his or hervoice shifted lower in pitch. This downward-shifted pitch is relaxingand pleasant, sort of like hearing James Earl Jones speak. If the user'sspeech-production muscles are abnormally tense, however, the user willhear his or her voice shifted higher in pitch.

U.S. Pat. No. 6,231,500, entitled Electronic Anti-Stuttering DeviceProviding Auditory Feedback and Disfluency-Detecting Biofeedback, issuedto Kehoe on May 15, 2001, is a continuation-in-part of U.S. Pat. No.5,794,203. The Kehoe '500 patent discloses micropower impulse radar(MIR) as an alternative to EMG biofeedback for monitoring a user'smuscle activity to detect disfluency. MIR is short-range radar, usingcommonly available microchips. Unlike other radar, MIR is small andinexpensive. A small sensor for monitoring laryngeal activity could betaped to a user's throat.

Conventional treatment techniques for treating stuttering typically donot use neurostimulation and/or drug delivery devices. These types ofdevices, however,.are capable of treating a number of neurologicaldisorders as well as symptoms of those disorders. In the context ofneurostimulators, an electrical lead having one or more electrodes istypically implanted near a specific site in the brain of a patient. Thelead is coupled to a signal generator that delivers electrical energythrough the electrodes and creates an electrical field causingexcitation of the nearby neurons to directly or indirectly treat theneurological disorder or symptoms of the disorder. In the context of adrug delivery system, a catheter coupled to a pump is implanted near atreatment site in the brain. Therapeutics are delivered to the treatmentsites in predetermined dosages through the catheter.

In an article entitled Cessation of Stuttering After Bilateral ThalamicInfarction, A.

Muroi et al. describe their observation of a patient who, afterparamedian thalamic infarction, experienced cessation of stuttering.Neurology, vol. 53, pp. 890-91 (September (1 of 2) 1999. In thisarticle, A. Muroi et al. state that neuroimaging studies indicate thatthe occlusion of a single artery, the mesencephalic artery, have givenrise to the infarction in the bilateral medial thalamus and rostralmesencephalic tegmentum. Further, in developmental stuttering, regionalcerebral blood flow (rCBF) was observed as relatively increased in themedial and lateral prefrontal areas and in the orbital cortices, andalso in the supplementary motor area (SMA) and the superior lateralpremotor cortex. A. Muroi et al. then discuss a study by Nagafuchi andTakahashi in which a patient started to stutter after an infarct in theSMA. Another article, by Abe et al., describes a case of stuttering-likerepetitive speech disorder after paramedian thalamomesencephalicinfarction. Yet another article, by Andy and Bhatnager, reported thatstuttering was elicited by destruction of the centromedian (CM) in onecase; they also found that stimulation of the same region alleviated theacquired stuttering in another case. The work reported by Andy andBhatnagar related only to adult onset, acquired stuttering, due to thepresence of cortical or subcortical pathologies (related to a centralpain syndrome), but did not involve the more common form ofdevelopmental stuttering. Further, there is no teaching in their work onthe application of DBS or drug delivery for the chronic treatment ofdevelopmental stuttering as a disorder of the motor system. Thedorsomedial (DM) nuclei and CM, which were involved in the case reportedby A. Muroi et al., are reciprocally connected to the lateral prefrontalarea and SMA, respectively. In light of these studies and the casereported by A. Muroi et al., the A. Muroi et al. article speculates thatdisordered function of the SMA-CM circuit or DM-lateral prefrontalcortex is responsible for developmental and acquired stuttering.Therefore, it may be possible to treat either developmental or acquiredstuttering by stimulation or drug delivery of the neural circuitsinvolved in stuttering.

Based on the foregoing, there is a need for stuttering-treatmenttechniques that use neural stimulation and/or drug delivery to targetthe neurological underpinnings of stuttering.

BRIEF SUMMARY OF THE INVENTION

The invention is directed toward various stuttering-treatment techniquesusing neural stimulation and/or drug delivery. In accordance withvarious inventive principles, a catheter is coupled to an implantablepump for infusing therapeutic dosages of at least one drug. At least oneimplantable electrode is coupled to a signal generator for deliveringelectrical stimulation. The invention may include various permutationsand/or combinations of the following steps: implanting the one or moreelectrodes adjacent to a first predetermined site in the brain;implanting the catheter so that the discharge portion lies adjacent to asecond predetermined site in the brain; coupling the proximal end of theimplanted electrode to the signal generator; coupling the catheter tothe pump; and operating the signal generator and the pump to stimulateor inhibit neurons of the first and second sites in the brain bydelivering electrical stimulation to the first site and by deliveringone or more drugs to the second predetermined site. The first and/orsecond predetermined sites can be: the supplementary motor area, theperisylvian speech-language cortex, the centromedian circuit, thedorsomedial nuclei, the lateral prefrontal circuit, the mesothalamicreticular formation, the basal ganglia, or other paramedian thalamic andmidbrain nuclei and fiber tracts including, but not limited to the rednucleus, the habenulointerpeduncular tract, the prerubral area, the zonaincerta, the thalamic primary sensory relay nuclei (e.g., ventrooralnucleus, ventrolateral nucleus), the parafasicular nucleus, and theintralaminar nucleus.

In accordance with the invention, the stuttering treatment may beperformed via periodic, such as once per week, transcranial magneticstimulation of a predetermined site of a patient's brain for apredetermined duration, such as 30 minutes. Thetranscranial-magnetic-stimulation site is delivered to: thesupplementary motor area, the perisylvian speech-language cortex, thecentromedian circuit, the dorsomedial nuclei, the lateral prefrontalcircuit, the mesothalamic reticular formation, the basal ganglia, orother paramedian thalamic and midbrain nuclei and fiber tractsincluding, but not limited to the red nucleus, thehabenulointerpeduncular tract, the prerubral area, the zona incerta, thethalamic primary sensory relay nuclei (e.g., ventrooral nucleus,ventrolateral nucleus), the parafasicular nucleus, and the intralaminarnucleus.

A system, in accordance with the invention, for therapeutically treatingstuttering in a patient is disclosed. The system includes: a signalgenerator; at least one implantable lead, coupled to the signalgenerator, for delivering electrical stimulation to at least onepredetermined site of the patient's brain; a sensor, located near thepatient's vocal folds, for generating a signal responsive to activity ofthe patient's vocal folds; a controller that adjusts at least onestimulation parameter in response to the signal from the sensor. Thecontroller could detect when the patient starts speaking and then startthe electrical stimulation in response to that patient having started tospeak. The controller could then stop the electrical stimulation apredetermined amount of time after the patient started speaking. Thesensor could be an electromyographic sensor, an electroglottographicsensor, or a microphone, which could be implanted within the patient'sbody. The controller could use a speech-recognition algorithm fordetecting stuttering based on the signal received from the sensor.

Other advantages, novel features, and further scope of applicability ofthe invention will be set forth in the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic illustration of a system for treatingstuttering illustrating a signal generator connected to an electrodeimplanted in a patient's brain.

FIG. 2 is a diagrammatic illustration of a stuttering-treatment systemincluding an implantable pump and catheter for delivering therapeuticsto predetermined sites in a patient's brain.

FIG. 3 is a diagrammatic illustration of a stuttering-treatment systemincluding a combined catheter and electrode implanted in a patient'sbrain.

FIG. 4 is a diagrammatic illustration of a stuttering-treatment systemin which a sensor is located near the patient's vocal folds and is usedto control the amount of treatment delivered.

FIG. 5 is a schematic block diagram of a microprocessor and relatedcircuitry for using the sensor to control drug delivery to the brain.

FIG. 6 is a flow chart illustrating a preferred form of a microprocessorprogram for using the sensor to control drug dosage administered to thebrain.

FIG. 7 is a schematic block diagram of a microprocessor and relatedcircuitry for using the sensor to control electrical stimulationadministered to the brain.

FIGS. 8-12 are flow charts illustrating a preferred form of amicroprocessor program for generating electrical stimulation pulses tobe administered to the brain.

FIG. 13 is a diagrammatic illustration of a stuttering-treatment systemin which a sensor is implanted in a patient's brain and is used tocontrol the amount of treatment delivered.

DETAILED DESCRIPTION OF THE INVENTION

The neurogenic basis of stuttering is not well understood, but ananalogy can be drawn between stuttering and motor tremor in a person'sextremities or axial musculature. It is know that in some forms oftremor the occurrence of abnormal neural activity in specific brainregions (e.g., thalamus) is associated with the presence of tremor. Itis also known that treatment of these regions with electricalstimulation or drug delivery can reduce or abolish tremor. Thestructures that are apparently involved in stuttering are thesupplementary motor area, (SMA), the centromedian circuit (CM circuit),the dorsomedial nuclei (DM nuclei), the lateral prefrontal circuit, andother paramedian thalamic and midbrain nuclei, and by analogy to tremor,it is hypothesized that abnormal neural activity in these structures andcircuits is associated with the presence of stuttering.

The thalamus and cortex are connected by a network of parallel neuralcircuits that send information in both directions to ultimately controlthoughts, emotions, motor behaviors, and various other higher levelfunctions. Each of the various types of functions appears to havediscrete anatomical circuit associated with them. If abnormal patternsof neural activity (e.g., too much or too little activity) arise in aspecific circuit due to disease, trauma, or developmental causes, theresult is often a clinical symptom associated with the specificfunctional area. For instance, obsessive-compulsive disorder is thoughtto be due to hyperactivity in the loop connecting orbital-frontal cortexwith the medial thalamus. Tremor in a specific body region appears toarise due to over activity in the loop between the basal ganglia,thalamus and the motor cortex subserving that body part. Similarly,stuttering may be related to abnormal activity in the basal ganglia andthalamo-cortical loops that control the production of speech.

It has been hypothesized that two such loops are involved in languageproduction and therefore in the dysfunction of stuttering: an “outer”linguistic loop, which controls the selection of speech information, andan “inner” motor loop that controls the actual production of speechsounds via control of the vocal apparatus. The linguistic loop appearsto be mediated by neural circuits in the perisylvian speech-languagecortex, and the motor loop by cortico-striatal-thalamo-corticalcircuits. A disruption in timing between these circuits has beensuggested as a possible mechanism of stuttering. By applying electricalstimulation and or drug delivery within these circuits, it may bepossible to re-establish the proper timing relationships and therebyreduce or eliminate stuttering.

For example, the supplementary motor area (SMA), part of the motor loop,can be thought of as generating a signal indicative of the intention todo something, such as begin speaking. That signal then gets passed tothe motor cortex, which is a part of the brain that sends acorresponding signal to a person's muscles, including a person's vocalcords, to do something, such as making speech sounds.

Disruption of the appropriate precursor signal from the SMA may beresponsible for a stutterer's inability to speak fluently when they arestarting to say something. Such a disruption may also be responsible fora stutterer's inability to break out of a loop in which the same soundis being unintentionally repeated and the inability to progress to thenext stage of speaking, which occurs in fluent speech.

This invention includes treatment techniques for ameliorating stutteringby influencing levels of activity in various neuronal loops associatedwith stuttering. These techniques include drug delivery, electrical andmagnetic stimulation, and/or closed loop feedback systems for detectingthe occurrence of speech or stuttering.

FIG. 1 is a diagrammatic illustration of a patient with an implant of aneurostimulation system employing an embodiment of the presentinvention. An implantable signal generator 16 produces stimulationsignals to various predetermined sites within a patient's brain, B. Thepredetermined sites may include the supplementary motor area (SMA), theperisylvian speech-language cortex, the centromedian circuit (CMcircuit), the dorsomedial nuclei (DM nuclei), the lateral prefrontalcircuit, the mesothalamic reticular formation, the basal ganglia andother paramedian thalamic and midbrain nuclei and fiber tractsincluding, but not limited to the red nucleus, thehabenulointerpeduncular tract, the prerubral area, the zona incerta, thethalamic primary sensory relay nuclei (e.g., ventrooral nucleus,ventrolateral nucleus), the parafasicular nucleus, and the intralaminarnucleus. Device 16 may take the form of a signal generator such as model7424 manufactured by Medtronic Inc. under the trademark Itrel II®.

As depicted in FIG. 1, a conductor 22 is implanted below the skin of apatient. The distal end of conductor 22 terminates in a lead 22A. Lead22A may take the form of any of the leads sold with Medtronic's Model7424 signal generator for stimulation of the brain. The proximal end ofconductor 22 is coupled to signal generator 16.

The distal end of lead 22A terminates in a stimulation electrode locatedat a predetermined area of the brain, B. The distal end of lead 22A isimplanted using stereotactic techniques that are well known by thoseskilled in the art. The physician determines the number of electrodesneeded for the particular treatment.

FIG. 2 is a diagrammatic illustration of a patient having an implant ofa drug delivery system employing an embodiment of the present invention.The system distributes a therapeutic agent to predetermined sites in thebrain selected by a physician. The system uses a pump 10 that can be animplantable pump like the Medtronic SynchroMed® pump or an externalpump. As depicted in FIG. 2, the pump 10 has a port 14 into which ahypodermic needle can be inserted to inject therapeutic to fill the pump10. In the system shown, the therapeutic is delivered from pump 10through a catheter port 20 into a catheter 222. Catheter 222 may beimplanted below the skin of a patient using well-known stereotacticplacement techniques and positioned to deliver the therapeutic to thepredetermined sites within the brain, B. The predetermined sites mayinclude the supplementary motor area (SMA), the perisylvianspeech-language cortex, the centromedian circuit (CM circuit), thedorsomedial nuclei (DM nuclei), the lateral prefrontal circuit, themesothalamic reticular formation, the basal ganglia and other paramedianthalamic and midbrain nuclei and fiber tracts including, but not limitedto the red nucleus, the habenulointerpeduncular tract, the prerubralarea, the zona incerta, the thalamic primary sensory relay nuclei (e.g.,ventrooral nucleus, ventrolateral nucleus), the parafasicular nucleus,and the intralaminar nucleus.

FIG. 3 is a diagrammatic illustration of a patient having an implant ofa neurological system employing an embodiment of the present invention.The system as shown in FIG. 3, illustrates a combined catheterelectrode, 322, that can distribute both stimulation signals andtherapeutics from the signal generator 16 and pump 10, respectively.

The combined catheter electrode 322 terminates with a cylindrical hollowtube 322A having a distal end implanted into a predetermined location ofa patient's brain, B. The distal end of tube 322A is implanted usingstereotactic techniques well known by those skilled in the art. Tube322A includes an outer cylindrical insulation jacket (not shown) and aninner insulation jacket (not shown) that defines a cylindrical catheterlumen. A multifular coil of wire, multiflar stranded wire or flexibleprinted circuit is embedded in tube 322A (not shown).

Trans-cranial magnetic stimulation could also be used as a means todeliver therapeutic stimulation to the nervous system to treatstuttering. This magnetic stimulation would tend to be more of aclinical application as opposed to a portable and/or human-implantabledevice. In accordance with the invention, a patient's stuttering couldbe treated periodically, such as once per week, via trans-cranialmagnetic stimulation of the supplementary motor area, (SMA), thecentromedian circuit (CM circuit), the dorsomedial nuclei (DM nuclei),the lateral prefrontal circuit, and other paramedian thalamic andmidbrain nuclei and fiber tracts including, but not limited to the rednucleus, the habenulointerpeduncular tract, the prerubral area, the zonaincerta, the thalamic primary sensory relay nuclei (e.g., ventrooralnucleus, ventrolateral nucleus), the parafasicular nucleus, and theintralaminar nucleus. The Magpro stimulator available from Medtronic,Inc. of Minneapolis Minn. is an example of a suitable magneticstimulator. Magnetic stimulators of this type are capable of causingelectrical current flow in particular regions of a patient's brainthereby activating specific neural structures or circuits. Such magneticstimulation has been used clinically as a diagnostic tool to evaluatethe condition of the motor system, and therapeutically to treatdisorders such as depression.

FIG. 4 shows the placement of a sensor, 130, near the vocal cords of apatient. The sensor 130 is coupled to the pump 10 via cable 132. Thevocal cords produce electrical signals, such as electromyographic (EMG)and electroglottographic (EGG) signals, that can be detected and used tocontrol the treatment method. For example, when a patient begins tospeak, sensor 130 could detect the vocal-fold activity and send a signalto the treatment device to indicate that therapy should begin. In thisembodiment, the treatment is delivered and continues to be deliveredcontinuously as the patient speaks. Alternatively, the sensor could becoupled to a microprocessor that contains speech recognition softwarestored in memory. The speech recognition software could be programmed todistinguish between stuttering and normal speech by detecting apredetermined number of repetitions of a speech pattern. For example,treatment could begin upon detecting three repetitions of a particularspeech pattern. The software could analyze an EMG or EGG waveform fromthe vocal folds, or signals from a microphone, either implanted orplaced externally on a person's neck near the person's vocal folds.

FIG. 13 shows the placement of a sensor, 1325, located in a specificregion of the brain to detect electroencephalogram (EEG) signals. Thesensor 1325 may be coupled to the pump 10 and the signal generator 16through the combined catheter electrode 1322. The EEG signals may bedetected and analyzed for abnormal activity related to stuttering withthe use of a microprocessor that contains EEG recognition softwarestored in memory. In this embodiment, treatment is delivered and maycontinue to be delivered based on the recorded electrical activity asseen by sensor 1325.

Several other techniques, which are well known in the art, could also beused in accordance with the invention for detecting speech disfluency.For instance, as described in more detail above, each of U.S. Pat. Nos.4,020,567, 5,794,203, and 6,231,500, which are incorporated herein byreference, disclose speech-disfluency-detection devices that could beused with this invention.

The amount and type of stimulation delivered in accordance with theinvention may be controlled based upon analysis of the output from asensor, such as sensor 130 shown in FIG. 4. Referring to FIG. 5, theoutput of a sensor 130, which could be an EEG, EMG or EGG sensor,micropower impulse radar, or a microphone as described above, is coupledby a cable 132 comprising conductors 134 and 135 to the input of analogto digital converter 140. Alternatively the output of the sensor 130could communicate through a “body bus” communication system as describedin U.S. Pat. No. 5,113,859 (Funke), which is assigned to Medtronic andwhich is incorporated herein by reference. Alternatively, the output ofan external feedback sensor 130 would communicate with the implantedpulse generator 16 or pump 10 through a telemetry down-link. The outputof the analog to digital converter 140 is connected to terminals EF2 BARand EF3 BAR. Such a configuration may be one similar to that shown inU.S. Pat. No. 4,692,147 (“'147 Patent”) except that before converter 140is connected to the terminals, the demodulator of the '147 patent(identified by 101) would be disconnected. A drug can be deliveredessentially continuously (within the constraints of the particulardelivery device being used) or it may be delivered during intermittentintervals coordinated to reflect the half-life of the particular agentbeing infused or with circadian rhythms. As an example, stuttering willtypically occur less frequently at night when the person is sleeping sothe drug delivery rates might be reduced to coincide with the hoursbetween 10 p.m. and 7 a.m.

An exemplary computer algorithm is shown in FIG. 6. Referring to FIGS. 5and 6, microprocessor 100 included within pump 10 reads converter 140 instep 150, and stores one or more values in RAM 102 a in step 152. Adosage is selected in step 154, and an appropriate time interval isselected in step 156. The selected dosage and interval of a drug is thendelivered through catheter 222 and tube 222A to the basal ganglia of thebrain as described in the '147 Patent.

For some types of sensors, a microprocessor and analog to digitalconverter will not be necessary. An appropriate elect filter can be usedto filter the output from sensor 130 to provide a control signal forsignal generator 16. An example of such a filter is found in U.S. Pat.No. 5,259,387 “Muscle Artifact Filter, Issued to Victor de Pinto on Nov.9, 1993, incorporated herein by reference.

A modified form of the ITREL II® signal generator can be used to achieveclosed-loop electrical stimulation, which is schematically depicted inFIG. 7. The output of the analog to digital converter 206 is connectedto a microprocessor 200 through a peripheral bus 202 including address,data and control lines. Microprocessor 200 processes the sensor data indifferent ways depending on the type of transducer in use. When thesignal on sensor 130 exceeds a sensor-signal threshold level stored in amemory 204, increasing amounts of stimulation will be applied through anoutput driver 224. The sensor-signal threshold level could be set suchthat the sensor signal will exceed the threshold whenever the person isspeaking. Alternatively, increasing amounts of stimulation could beapplied through the output driver 224 when speech-processing softwaredetects a speech pattern that is likely to correspond to stuttering.

Programming a value to a programmable frequency generator 208, using bus202, controls the stimulus pulse frequency. The programmable frequencygenerator provides an interrupt signal to microprocessor 200 through aninterrupt line 210 when each stimulus pulse is to be generated. Thefrequency generator may be implemented by model CDP1878 sold by HarrisCorporation. The amplitude for each stimulus pulse is programmed to adigital to analog converter 218 using bus 202. The analog output isconveyed through a conductor 220 to an output driver circuit 224 tocontrol stimulus amplitude. Microprocessor 200 also programs a pulsewidth control module 214 using bus 202. The pulse width control providesan enabling pulse of duration equal to the pulse width via a conductor.Pulses with the selected characteristics are then delivered from signalgenerator 16 through cable 22 and lead 22A to the target locations of abrain B.

Microprocessor 200 executes an algorithm shown in FIGS. 8-12 in order toprovide stimulation with closed loop feedback control. At the time thestimulation signal generator 16 or alternative device in which thestimulation and infusion functions are combined is implanted, theclinician programs certain key parameters into the memory of theimplanted device via telemetry. These parameters may be updatedsubsequently as needed. Step 400 in FIG. 8 indicates the process offirst choosing whether the neural activity at the stimulation site is tobe blocked or facilitated (step 400(1)) and whether the sensor locationis one for which an increase in the neural activity at that location isequivalent to an increase in neural activity at the stimulation targetor vice versa (step 400(2)). Next the clinician must program the rangeof release for pulse width (step 400(3)), amplitude (step 400(4)) andfrequency (step 400(5)) which signal generator 16 may use to optimizethe therapy. The clinician may also choose the order in which theparameter changes are made (step 400(6)). Alternatively, the clinicianmay elect to use default values.

The algorithm for selecting parameters is different depending on whetherthe clinician has chosen to block the neural activity at the stimulationtarget or facilitate the neural activity. FIG. 8 details steps of thealgorithm to make parameter changes.

The algorithm uses the clinician programmed indication of whether theneurons at the particular location of the stimulating electrode are tobe facilitated or blocked in order to decide which path of the parameterselection algorithm to follow (step 420, FIG. 9). If the neuronalactivity is to be blocked, signal generator 16 first reads the feedbacksensor 130 in step 421. If the sensor values indicate a likelihood thatthe activity in the neurons is too high (step 450), for instance, ifspeech processing software detects a speech pattern likely to correspondto stuttering, the algorithm in this embodiment first increases thefrequency of stimulation in step 424 provided this increase does notexceed the preset maximum value set by the physician. Step 423 checksfor this condition. If the frequency parameter is not at the maximum,the algorithm returns to step 421 through path 421A to monitor-the feedback signal from sensor 130.

If the frequency parameter is at the maximum, the algorithm nextincreases the pulse width in step 426 (FIG. 10), again with thecondition that this parameter has not exceeded the maximum value aschecked for in step 451 through path 423A. Not having reached maximumpulse width, the algorithm returns to step 421 to monitor the feedbacksignal from sensor 130. Should the maximum pulse width have beenreached, the algorithm next increases amplitude in a like manner asshown in steps 427 and 428. In the event that all parameters reach themaximum, a notification message is set in step 429 to be sent bytelemetry to the clinician indicating that device 16 is unable to reduceneural activity to the desired level.

If, on the other hand, the stimulation electrode is placed in a locationwhich the clinician would like to activate in order to alleviatestuttering, the algorithm would follow a different sequence of events.In the preferred embodiment, the frequency parameter would be fixed at avalue chosen by the clinician to facilitate neuronal activity in step430 (FIG. 11) through path 420A. In steps 431 and 432 the algorithm usesthe values of the feedback sensor to determine if neuronal activity isbeing adequately controlled. In this case, inadequate control indicatesthat the neuronal activity of the stimulation target is too low.Neuronal activity is increased by first increasing stimulation amplitude(step 434) provided it doesn't exceed the programmed maximum valuechecked for in step 433. When maximum amplitude is reached, thealgorithm increases pulse width to its maximum value in steps 435 and436 (FIG. 12). A lack of adequate alteration of the symptoms of theneurological disorder, even though maximum parameters are used, isindicated to the clinician in step 437. After steps 434, 436 and 437,the algorithm returns to step 431 through path 43 1A, and the feedbacksensor is read again.

It is desirable to reduce parameter values to the minimum level neededto establish the appropriate level of neuronal activity in, for example,the target brain nucleus. Superimposed on the algorithm just describedis an additional algorithm to readjust all the parameter levels downwardas far as possible. In FIG. 8, steps 410 through 415 constitute themethod to do this. When parameters are changed, a time is reset in step415. If there is no need to change any stimulus parameters before thetimer has counted out, then it may be possible due to changes inneuronal activity to reduce the parameter values and still maintainappropriate levels of neuronal activity in the target neurons. At theend of the programmed time interval, signal generator 16 tries reducinga parameter in step 413 to determine if control is maintained. If it is,the various parameter values will be ratcheted down until such time asthe sensor values again indicate a need to increase them. While thealgorithms in FIGS. 8-12 follow the order of parameter selectionindicated, other sequences may be programmed by the clinician.

While the invention has been described with respect to specific examplesincluding presently preferred modes of carrying out the invention, thoseskilled in the art will appreciate that there are numerous variationsand permutations of the above described systems and techniques that fallwithin the spirit and scope of the invention as set forth in theappended claims and their equivalents.

1. A method of therapeutically treating stuttering via transcranialmagnetic stimulation, the method comprising: periodically stimulating,for a predetermined duration, a first predetermined site of a patient'sbrain using transcranial magnetic stimulation, wherein the firstpredetermined site is selected from the group consisting of: thesupplementary motor area, the perisylvian speech-language cortex, thecentromedian circuit, the dorsomedial nuclei, the lateral prefrontalcircuit, the mesothalamic reticular formation, the basal ganglia, andother paramedian thalamic and midbrain nuclei and fiber tractsincluding, the red nucleus, the habenulointerpeduncular tract, theprerubral area, the zona incerta, the thalamic primary sensory relaynuclei, the ventrooral nucleus, the ventrolateral nucleus, theparafasicular nucleus, and the intralaminar nucleus.
 2. The method ofclaim 1, wherein the predetermined duration of transcranial magneticstimulation is approximately 30 minutes.
 3. The method of claim 2,wherein the transcranial magnetic stimulation is periodically performedapproximately once per week.
 4. The method of claim 1, wherein thetranscranial magnetic stimulation is periodically performedapproximately once per week.
 5. The method of claim 1, wherein the firstpredetermined site is the supplementary motor area.
 6. The method ofclaim 1, wherein the first predetermined site is the perisylvianspeech-language cortex.
 7. The method of claim 1, wherein the firstpredetermined site is the centromedian circuit.
 8. The method of claim1, wherein the first predetermined site is the dorsomedial nuclei. 9.The method of claim 1, wherein the first predetermined site is thelateral prefrontal circuit.
 10. The method of claim 1, wherein the firstpredetermined site is the mesothalamic reticular formation.
 11. Themethod of claim 1, wherein the first predetermined site is the basalganglia.
 12. The method of claim 1, wherein the first predetermined siteis at least one of the paramedian thalamic and midbrain nuclei and fibertracts.
 13. The method of claim 12 wherein the at least one of theparamedian thalamic and midbrain nuclei and fiber tracts is selectedfrom the group consisting of: the red nucleus, thehabenulointerpeduncular tract, the prerubral area, the zona incerta, thethalamic primary sensory relay nuclei, the ventrooral nucleus, theventrolateral nucleus, the parafasicular nucleus, and the intralaminarnucleus.
 14. The method of claim 1 wherein the step of periodicallystimulating, for a predetermined duration, a first predetermined site ofa patient's brain using transcranial magnetic stimulation causeselectrical current flow in the first predetermined site.